More than 100 million dental restorations are performed each year, and at least 60% of those use polymerizable composites. Despite their ubiquitous presence in dentistry, polymerizable composites suffer from significant structural problems. Based on resin chemistry developed nearly 50 years ago, radically polymerizable dimethacrylate monomers have remained the monomers of choice in these composites.
The bisphenol A dimethacrylate (BisGMA)-based methacrylate resin is cured by light exposure, which causes radical formation. These radicals then mediate a chain-growth polymerization and conversion of methacrylates into crosslinked polymers, with the associated shrinkage and stress arising from conversion of monomer to polymer. Though most considerations of new dental restorative materials have focused on methacrylate modifications, this curing approach is flawed in ways not readily addressed without changing the composite nature. In particular, chain growth leads to a significant amount of residual, unreacted double bonds (and hence monomers) at the end of the polymerization. These monomers can be extracted and lead to non-desirable biological interactions. Further, methacrylates comprise esters that are unstable towards enzymes and high or low pH. Thus, most methacrylate-based systems may be limited in their ability for significant performance improvements.
Thus, problems inherent to the BisGMA system include, among others, the presence of extractable, unreacted monomer following cure, monomer and composite degradation, polymerization shrinkage and induced stresses, a lack of mechanical toughness and wear, and moisture uptake. The common result of these problems is premature failure of composites, resulting from secondary caries or mechanical failure of the bulk or the interface. With average lifetimes of only about 8 years for current restorative materials, there is great need to develop novel and improved composite materials for dental restorations.
The “click” reaction paradigm is centered on the development and implementation of robust reactions that proceed with reliable control over the products formed. A “click” reaction should have the following characteristics: the reaction involves minimal set-up effort and the starting materials are readily available; the reaction is high yielding, proceeding with high stereospecificity and high atom economy; the reaction is run solvent-free or in a benign solvent (preferably water); the product can be easily isolated by crystallization or distillation, preparative chromatography not being required; the by-products are easily removed and non-toxic; the reaction is physiologically compatible; and there is a large thermodynamic driving force (>84 kJ/mol) to favor the formation of a single reaction product.
One reaction that meets most of these criteria is the azide-alkyne Huisgen cycloaddition, which is a 1,3-dipolar cycloaddition between an azide and a terminal or internal alkyne to give a 1,2,3-triazole (Huisgen, 1961, Proc. Chem. Soc. London:357; Kolb et al., 2001, Angew. Chem.-Int. Edit. 40(11):2004-21).
A notable variant of the Huisgen 1,3-dipolar cycloaddition is the copper(I) catalyzed (or Cu(I)-catalyzed) variant, in which organic azides and terminal alkynes are united to afford 1,4-regioisomers of 1,2,3-triazoles as sole products (Tornoe et al., 2002, J. Org. Chem. 67:3057-64). While the Cu(I)-catalyzed variant gives rise to a triazole from a terminal alkyne and an azide, formally it is not a 1,3-dipolar cycloaddition and thus should not be termed a Huisgen cycloaddition. This reaction is known as the Cu(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC).
CuAAC is ubiquitous and highly efficient in an ever increasing number of synthetic methodologies and applications, including bioconjugation (Wang et al., 2003, J. Am. Chem. Soc. 125(11):3192; El-Sagheer & Brown, 2010, Chem. Soc. Rev. 39(4):1388); labeling (Macpherson et al., 2007, Nature 445(7127):541; Cohen et al., 2007, Nat. Chem. Biol. 3(3):156); surface functionalization (Spruell et al., 2008, Angew. Chem.-Int. Edit. 47(51):9927); dendrimer synthesis (Peng et al., 2004, Angew. Chem.-Int. Edit. 43(30):3928); polymer synthesis (DeForest et al., 2009, Nat. Mat. 8(8):659); and polymer modification (Matyjaszewski & Tsarevsky, 2009, Nat. Chem. 1(4):276). The diverse implementation of the CuAAC reaction is due to its simplicity, capability of high yield, fast reaction kinetics, orthogonal reactivity, and tolerance to a wide variety of solvent conditions. The CuAAC reaction may be run in a variety of solvents, such as aqueous solvents and (partially or fully) miscible organic solvents. The CuAAC reaction may be performed using commercial sources of Cu(I) such as cuprous bromide or iodide, or in situ sources of Cu(I), such as a mixture of Cu(II) (e.g. copper(II) sulfate) and a reducing agent (e.g. sodium ascorbate).
There is a need in the art to develop novel monomer systems that afford useful composite compositions once polymerized. Such polymerized composite compositions should have superior chemical and physical properties, allowing for their use in challenging applications, such as dental restorations. The present invention fulfills these needs.